VPAC1 receptors for imaging breast cancer: a feasibility study.

UNLABELLED: VPAC1 encodes G-protein-coupled receptors expressed on all breast cancer (BC) cells at the onset of the disease, but not on benign lesions. Our extensive preclinical studies have shown that (64)Cu-TP3805 has a high affinity for VPAC1, is stable in vivo, and has the ability to distinguish spontaneously grown malignant BC masses from benign lesions. Our long-term goal is to develop (64)Cu-TP3805 as an agent to perform in vivo histology, to distinguish malignant lesions from benign masses noninvasively and thereby avoid patient morbidity and the excess economic costs of benign biopsies. METHODS: (18)F-FDG obtained commercially served as a control. (64)Cu-TP3805 was prepared using a sterile kit containing 20 µg of TP3805. Radiochemical purity and sterility were examined. Nineteen consenting women with histologically proven BC were given 370 MBq of (18)F-FDG. One hour later, 6 of these patients were imaged with PET/CT and 13 with positron emission mammography (PEM). Two to 7 d later, 6 PET/CT patients received 111 MBq (± 10%) (n = 2), 127 MBq (± 10%) (n = 2), or 148 MBq (± 10%) (n = 2) of (64)Cu-TP3805 and were imaged 2 and 4 h later. Thirteen PEM patients received 148 MBq (± 10%) of (64)Cu-TP3805 and were imaged 15 min, 1 h, 2 h, and 4 h later. Standardized uptake value (SUV) was calculated for PET/CT patients, and PUV/BGV (PEM uptake value/background value) was calculated for PEM patients. Tumor volume was also calculated. RESULTS: The radiochemical purity of (64)Cu-TP3805 was 97% ± 2%, and specific activity was 44.4 GBq (1.2 Ci)/µmol. In 19 patients, a total of 24 lesions were imaged (15 invasive ductal carcinoma, 1 high-grade mammary carcinoma, 3 lobular carcinoma, 1 invasive papilloma, and 4 sentinel lymph nodes). All lesions were unequivocally detected by (64)Cu-TP3805 and by (18)F-FDG. The average tumor volume as determined by PET/CT with (64)Cu-TP3805 was 90.6% ± 16.1% of that with (18)F-FDG PET/CT, and the average SUV was 92% ± 26.4% of that with (18)F-FDG. For PEM, the tumor volume with (64)Cu-TP3805 was 113% ± 37% of that with (18)F-FDG and the PUV/BGV ratio was 97.7% ± 24.5% of that with (18)F-FDG. CONCLUSION: (64)Cu-TP3805 is worthy of further investigation in patients requiring biopsy of suggestive imaging findings, to further evaluate its ability to distinguish malignant lesions from benign masses noninvasively.

Drug dependence involving prednisone: two cases and a review of the literature.

Dependence is an unusual, but potentially serious complication of corticosteroid use. Two cases of prednisone dependence are reviewed; the first involving a patient with inflammatory orbital pseudotumor who developed a dependent pattern of prednisone use that persisted years after the resolution of the acute episode. The second case involves a patient with factitious disorder who attempted to obtain corticosteroids from multiple clinicians, despite the absence of any clinical indication for them, manipulating elements of her medical history to influence the prescription of corticosteroids. Both patients exhibited tolerance and withdrawal symptoms, and both developed serious systemic effects from the corticosteroids, including cataracts, diabetes mellitus, and cushingoid signs. Both patients also exhibited dependence upon other substances. A MEDLINE search was conducted, and the case literature regarding corticosteroid dependence was reviewed. Twenty-six cases of potential corticosteroid dependence were identified, and 22/26 (85%), retrospectively, met criteria for DSM-IV substance dependence involving corticosteroids. Prednisone was the most frequently implicated corticosteroid, but cases involving ACTH, cortisone, and high-dose inhaled dexamethasone and beclomethasone were also identified. Asthma was the most common underlying medical condition for which the corticosteroids were prescribed, but a variety of allergic and inflammatory conditions were also reported. Corticosteroids may induce dependence based on their propensity to induce euphoria as well as a characteristic withdrawal syndrome, in addition to directly influencing reward circuitry. Clinicians should be aware of the possibility of prednisone dependence when confronted with patients who exhibit vigorous insistence on corticosteroids out of proportion to objective signs and symptoms of inflammation.